Low Pain Tolerance Is Associated With Coronary Angiography, Coronary Artery Disease, and Mortality: The Tromsø Study.

Background The initial presentation to coronary angiography and extent of coronary artery disease (CAD) vary greatly among patients, from ischemia with no obstructive CAD to myocardial infarction with 3-vessel disease. Pain tolerance has been suggested as a potential mechanism for the variation in presentation of CAD. We aimed to investigate the association between pain tolerance, coronary angiography, CAD, and death. Methods and Results We identified 9576 participants in the Tromsø Study (2007-2008) who completed the cold-pressor pain test, and had no prior history of CAD. The median follow-up time was 10.4 years. We applied Cox-regression models with age as time-scale to calculate hazard ratios (HR). More women than men aborted the cold pressor test (39% versus 23%). Participants with low pain tolerance had 19% increased risk of coronary angiography (HR, 1.19 [95% CI, 1.03-1.38]) and 22% increased risk of obstructive CAD (HR, 1.22 [95% CI, 1.01-1.47]) adjusted by age as time-scale and sex. Among women who underwent coronary angiography, low pain tolerance was associated with 54% increased risk of obstructive CAD (HR, 1.54 [95% CI, 1.09-2.18]) compared with high pain tolerance. There was no association between pain tolerance and nonobstructive CAD or clinical presentation to coronary angiography (ie, stable angina, unstable angina, and myocardial infarction). Participants with low pain tolerance had increased risk of mortality after adjustment for CAD and cardiovascular risk factors (HR, 1.40 [95% CI, 1.19-1.64]). Conclusions Low cold pressor pain tolerance is associated with a higher risk of coronary angiography and death.

Small and large vessel disease in persons with unrecognized compared to recognized myocardial infarction: The Tromsø Study 2007-2008.

BACKGROUND: Unrecognized myocardial infarction (MI) is a frequent condition with unknown underlying reason. We hypothesized the lack of recognition of MI is related to pathophysiology, specifically differences in underlying small and large vessel disease. METHODS: 6128 participants were examined with retinal photography, ultrasound of the carotid artery and a 12­lead electrocardiography (ECG). Small vessel disease was defined as narrower retinal arterioles and/or wider retinal venules measured on retinal photographs. Large vessel disease was defined as carotid artery pathology. We defined unrecognized MI as ECG-evidence of MI without a clinically recognized event. We analyzed the cross-sectional relationship between MI recognition and markers of small and large vessel disease, adjusted for age and sex. RESULTS: Unrecognized MI was present in 502 (8.2%) and recognized MI in 326 (5.3%) of the 6128 participants. Compared to recognized MI, unrecognized MI was associated with small vessel disease indicated by narrower retinal arterioles (OR 1.66, 95% CI 1.05-2.62, highest vs. lowest quartile). Unrecognized MI was less associated with wider retinal venules (OR 0.55, 95% CI 0.35-0.87, lowest vs. highest quartile). Compared to recognized MI, unrecognized MI was less associated with large vessel disease indicated by presence of plaque in the carotid artery (OR for presence of carotid artery plaque in unrecognized MI 0.51, 95% CI 0.37-0.69). No significant sex interaction was present. CONCLUSIONS: Unrecognized MI was more associated with small vessel disease and less associated with large vessel disease compared to recognized MI. These findings suggest that the pathophysiology behind unrecognized and recognized MI may differ.

Electrocardiographic unrecognized myocardial infarction does not improve prediction of cardiovascular events beyond traditional risk factors. The Tromsø Study.

Background Unrecognized myocardial infarction (MI) is a frequent and intriguing entity associated with a similar risk of death as recognized MI. Previous studies have not fully addressed whether the poor prognosis is explained by traditional cardiovascular risk factors. We investigated whether electrocardiographically detected unrecognized MI was independently associated with cardiovascular events and death and whether it improved prediction for future MI in a general population. Design Prospective cohort study. Methods We studied 5686 women and men without clinically recognized MI at baseline in 2007-2008. We assessed the risk of future MI, stroke and all-cause mortality in persons with unrecognized MI compared with persons with no MI during 31,051 person-years of follow-up. Results In the unadjusted analyses, unrecognized MI was associated with increased risk of future recognized MI (hazard ratio 1.84, 95% confidence interval (CI) 1.15-2.96) and all-cause mortality (hazard ratio 1.78, 95% CI 1.21-2.61), but not stroke (hazard ratio 1.09, 95% CI 0.56-2.17). The associations did not remain significant after adjustment for traditional risk factors (hazard ratio 1.25, 95% CI 0.76-2.06 and hazard ratio 1.38, 95% CI 0.93-2.05) for MI and all-cause mortality respectively. Unrecognized MI did not improve risk prediction for future recognized MI using the Framingham Risk Score ( p = 0.96) or the European Systematic COronary Risk Evaluation ( p = 0.65). There was no significant sex interaction regarding any of the endpoints. Conclusion Electrocardiographic unrecognized MI was not significantly associated with future risk of MI, stroke or all-cause mortality in the general population after adjustment for the traditional cardiovascular risk factors, and it did not improve prediction of future MI.

Pain Tolerance in Persons With Recognized and Unrecognized Myocardial Infarction: A Population-Based, Cross-Sectional Study.

BACKGROUND: Unrecognized myocardial infarction (MI) is a prevalent condition associated with a similar risk of death as recognized MI. It is unknown why some persons experience MI with few or no symptoms; however, one possible explanation is attenuated pain sensitivity. To our knowledge, no previous study has examined the association between pain sensitivity and recognition of MI. METHODS AND RESULTS: We conducted a population-based cross-sectional study with 4849 included participants who underwent the cold pressor test (a common experimental pain assay) and ECG. Unrecognized MI was present in 387 (8%) and recognized MI in 227 (4.7%) participants. Participants with unrecognized MI endured the cold pressor test significantly longer than participants with recognized MI (hazard ratio for aborting the cold pressor test, 0.64; CI, 0.47-0.88), adjusted for age and sex. The association was attenuated and borderline significant after multivariable adjustment. The association between unrecognized MI and lower pain sensitivity was stronger in women than in men, and statistically significant in women only, but interaction testing was not statistically significant (P for interaction=0.14). CONCLUSIONS: Our findings suggest that persons who experience unrecognized MI have reduced pain sensitivity compared with persons who experience recognized MI. This may partially explain the lack of symptoms associated with unrecognized MI.